Responsive MXene nanovehicles deliver CRISPR/Cas12a for boolean logic-controlled gene editing  

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作  者:Song Wang Zhenhua Zhang Rui Tang Fang He Yan Huang Zhou Nie Chunyang Lei 

机构地区:[1]Department State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Chemistry and Chemical Engineering,Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology,Hunan University,Changsha 410082,China [2]Hubei Yangtze Memory Laboratories,Wuhan 430205,China

出  处:《Science China Chemistry》2022年第11期2318-2326,共9页中国科学(化学英文版)

基  金:supported by the National Key Research and Development Program of China (2020YFA0907500);the National Natural Science Foundation of China (22034002, 21974038, 21725503, 22074034);the Natural Science Foundation of Hunan Province (2022JJ20004);。

摘  要:Programmable and precise regulation of genetic information is crucial in bioengineering and biomedicine;however, it remains challenging to implement this objective. Here we deployed DNA-functionalized MXenes as a smart delivery system for spatiotemporally controllable genome editing. The MXene nanovehicles rationally integrated photothermal effect with nucleic acid strand displacement reaction, thereby allowing for the binary logic gate-controlled release of Cas ribonucleoprotein complexes in response to different input patterns of NIR light and nucleic acids. This system was highly programmable and could be harnessed to construct 2-input(AND, OR, and N-IMPLY) and 3-input(AND/OR and N-IMPLY/OR) logic gates for precise gene editing in mammalian cells. Moreover, an AND logic gate-controlled delivery system achieved selective induction of tumor cell death in a xenograft mice model using tissue-penetrating NIR light and cancer-relevant microRNA as the inputting cues.Therefore, the MXene nanovehicles adopted both the external and endogenous signals as the stimuli to precisely control gene editing under logic computation, presenting a helpful strategy for therapeutic genome editing.

关 键 词:Mxenes boolean logic gates CRSIPR/Cas12a gene editing nanovehicles 

分 类 号:TB383.1[一般工业技术—材料科学与工程] Q78[生物学—分子生物学]

 

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